Modular targeted therapeutic agents and methods of making same

a targeted therapeutic agent and module technology, applied in the field of modules targeted therapeutic agents and methods of making same, can solve the problems of potentially significant health risks of exposure to such agents, and achieve the effects of enhancing efficacy, rapid and efficient identification, isolation and production, and low cost methods

Active Publication Date: 2013-07-18
PROTEONOVA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0046]In several embodiments, methods provided herein utilize novel techniques for linking proteins to their corresponding mRNAs, and screening the protein-mRNA complexes for binding to a target associated with a particular soluble agent. In some embodiments, the identified proteins having high affinity for a soluble agent of interest are preferably isolated and linked to one or more immune modulators, to produce a variety of targeted therapeutics. Advantageously, the rapid and efficient identification, isolation, and production of proteins capable of recognizing targets of interest provides effective, low cost methods for the production of patient- and/or condition-specific therapeutics. In various embodiments, methods provided herein beneficially all

Problems solved by technology

Also, numerous toxins, venoms, chemical agents, and other agents that alter physiological b

Method used

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  • Modular targeted therapeutic agents and methods of making same
  • Modular targeted therapeutic agents and methods of making same
  • Modular targeted therapeutic agents and methods of making same

Examples

Experimental program
Comparison scheme
Effect test

example 1

Production of the SATA

[0197]One skilled in the art will understand that the SATA can be produced in a number of different ways. The protocols described below in the following examples can be used for SATAs that have both a puromycin and a crosslinker on the tRNA, or that have a puromycin on the tRNA and a crosslinker on the mRNA. Where the crosslinker is on the mRNA, Example 4, below, provides guidance. The following protocol is also instructive for Linking tRNA Analogs, in the sense that Linking tRNA Analogs also, in a preferred embodiments, have a crosslinker on the tRNA.

[0198]For example, in a preferred embodiment, three fragments (FIG. 1) were purchased from a commercial source (e.g., Dharmacon Research Inc., Boulder, Colo.). Modified bases and a fragment 3 with a pre-attached puromycin on its 3′ end and a PO4 on its 3′ end were included, all of which were available commercially. Three fragments were used to facilitate manipulation of the fragment 2 in forming the monoadduct.

[01...

example 2

Production Of Psoralenated Furan Sided Monoadducts

[0207]UV Light Exposure of RNA: DNA Hybrids

[0208]Equal volumes of 3 ng / ml RNA:cRNA hybrid segments and of 10 μg / ml HMT both comprised of 50 mM NaCl were transferred into a new 1.5 ml capped polypropylene microcentrifuge tube and incubated at 37° C. for 30 minutes in the dark. This was then transferred onto a new clean culture dish. This was positioned in a photochemical reactor (419 nm peak Southern New England Ultraviolet Co.) at a distance of about 12.5 cm so that irradiance was ˜6.5 mW / cm2 and irradiated for 60-120 minutes.

[0209]Removal of Low Molecular Weight Protoproducts

[0210]1000 of chloroform-isoamyl alcohol (24:1) was pipetted and mixed by vortex. The mixture was centrifuged for 5 minutes at 15000×g in a microcentrifuge tube. The chloroform-isoamyl alcohol layer was removed with a micropipette. The chloroform-isoamyl alcohol extraction was repeated once again. Clean RNA was precipitated out of the solution.

[0211]Alcohol Prec...

example 3

Production of the SATA Using Pseudouridine

[0275]As discussed above, one skilled in the art will appreciate that the SATA, Linking tRNA Analog and Nonsense Suppressor tRNA can be produced in a number of different ways. FIG. 5 shows the chemical structures for uridine and pseudouridine. Pseudouridine is a naturally occurring base found in tRNA that forms hydrogen bonds just as uridine does, but lacks the 5-6 double bond that is the target for psoralen. Pseudouridine, as used herein, shall include the naturally occurring base and any synthetic analogs or modifications. In a preferred embodiment, the SATA was produced using pseudouridine. Linking tRNA Analog can also be produced using pseudouridine. Specifically, in a preferred embodiment, three fragments (FIG. 1) were purchased from a commercial source (Dharmacon Research Inc., Boulder, Colo.). Modified bases and a fragment 3 (“Fragment 3”) with a pre-attached puromycin on its 3′ end and a PO4 on its 3′ end were included, all of which ...

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Abstract

Provided herein are methods for making targeted therapeutics. In several embodiments, the therapeutics are directed against soluble agents such as toxins, venoms, and/or other factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments, the therapeutics are directed to patient-specific disease markers. In several embodiments, the methods comprise screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent.

Description

RELATED CASES[0001]The contents of each priority document listed in the accompanying Application Data Sheet is incorporated in its entirety by reference herein. This application also incorporates by reference the sequence listing submitted as ASCII text filed concurrently via EFS-Web. The Sequence Listing is provided as a file entitled “ST25 Sequence Listing—PRONOV.009P1”, created on Mar. 1, 2013 and which is 11.4 kilobytes in size.BACKGROUND[0002]1. Field of the Invention[0003]The present invention relates to methods for making therapeutics tailored to individual patients or sub-populations of patients. Several embodiments relate to methods for making therapeutics that target soluble agents such as toxins, venoms, and / or other factors that alter physiological biopathways. Methods of using such targeted therapeutics are also provided, for example using therapeutics targeting soluble agents to treat patients or patient populations that have been exposed to such agents to reduce, elim...

Claims

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Application Information

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IPC IPC(8): A61K39/395
CPCA61K39/395C12N15/1075C12N15/1068C12P19/34C07K16/30C07K2319/30C12N15/62C07K2319/00C12N15/1062G01N33/6845C40B30/04G01N33/531C07K14/00
Inventor WILLIAMS, RICHARD B.GUERRERO, ROBERT
Owner PROTEONOVA
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